title: Hepatitis B virus X protein impedes the DNA repair via its association with transcription factor, TFIIH.
abstract: BACKGROUND
  Hepatitis B virus (HBV) infections play an important role in the development of hepatocellular carcinoma (HCC). HBV X protein (HBx) is a multifunctional protein that can modulate various cellular processes and plays a crucial role in the pathogenesis of HCC. HBx is known to interact with DNA helicase components of TFIIH, a basal transcriptional factor and an integral component of DNA excision repair.
  
  
  RESULTS
  In this study, the functional relevance of this association was further investigated in the context to DNA repair. By site-directed mutagenesis HBx's critical residues for interaction with TFIIH were identified. Similarly, TFIIH mutants lacking ATPase domain and the conserved carboxyl-terminal domain failed to interact with HBx. Yeast and mammalian cells expressing HBx(wt) conferred hypersensitivity to UV irradiation, which is interpreted as a basic deficiency in nucleotide excision repair. HBx(mut120) (Glu to Val) was defective in binding to TFIIH and failed to respond to UV.
  
  
  CONCLUSIONS
  We conclude that HBx may act as the promoting factor by inhibiting DNA repair causing DNA damage and accumulation of errors, thereby contributing to HCC development.
authors.affiliation: NUST Center of Virology and Immunology, National University of Science and Technology, Academic Block, Kashmir Highway, H-12 Islamabad, Pakistan. ishtiaq80262@yahoo.com
authors.forename: Ishtiaq
authors.initials: I
authors.lastname: Qadri
authors.forename: Kaneez
authors.initials: K
authors.lastname: Fatima
authors.forename: Hany
authors.initials: H
authors.lastname: AbdeL-Hafiz
mesh_terms: D001665:Binding Sites; D004260:DNA Repair; D006515:Hepatitis B virus / Q000235:genetics; D022781:Hepatocytes / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D054730:Protein Interaction Domains and Motifs; D012441:Saccharomyces cerevisiae / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D051758:Transcription Factor TFIIH / Q000378:metabolism*; D014466:Ultraviolet Rays; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D051758:Transcription Factor TFIIH